This invention relates to polyurethane polymers having a combination of specific properties that makes these polymers especially suitable for long term implantation within a living body. The biostable polymers of this invention possess, inter alia, a low modulus of elasticity and a high ultimate tensile strength as well as the biostability to permit them to be implanted within a living body and exhibit little or no degradation over extended periods.
Extensive investigations have been undertaken over many years to find materials that will be biologically and chemically stable towards body fluids and body tissue. This area of research has become increasingly important with the development of various objects and articles which can be implanted within a living body, such as pacemaker leads, vascular grafts, mammary prostheses, pacemaker bodies, probes, cannulas, catheters, and the like.
Polyurethanes have become particularly crucial in the production of pacemaker leads which provide the pathway for the pacemaker energy output into the heart. The lead insulation may be the most simple looking part of the device, but is one of the most critical components. While it is not unreasonable for a patient to require replacements of the pacemaker energy supply units during his/her life, the insertion of the lead is the more critical portion of the operation and thus must be expected to remain unchanged and provide absolute reliability for periods of 15 years or longer. Unfortunately, the currently available pacemaker leads are known to biodegrade. The biodegradation is characterized by surface fissuring caused by oxidation of the conventional ether linkages present within the polyurethane molecular chain. The oxidation leads to chain cleavage, reduction in molecular weight and eventual catastrophic mechanical failure. Surface fissuring is a progressive phenomenon which starts as surface microfissures which continue to propagate into the bulk, eventually resulting in loss of electrical insulating capacity and inappropriate heart muscle stimulation. The development of a polyurethane polymer in which the onset of microscopic surface fissuring is substantially delayed and/or prevented is desirable to develop improved pacemaker leads.
Vascular grafts, particularly arterial grafts having diameters of 4 mm or less and suitable for the replacement of coronary arteries, represent a further potential large market for polyurethane polymers if only a suitable material existed. It is generally accepted that dacron and polytetrafluoroethylene grafts, while having sufficient tensile strength to be suitable for use in large and medium diameter grafts, fail when used as small diameter grafts due to their excessive stiffness, i.e. they do not exhibit a sufficiently low elastic modulus. Most currently available polyurethanes, as well as being biodegradable, suffer from a similar problem in that when they have good tensile strengths of about 4500 psi they also have high moduli. There is thus a need for a biostable polyurethane polymer which has both a high tensile strength and a low elastic modulus and which can be formed into a small diameter vascular graft.
Mammary prostheses today are generally made of a silicone bag containing a silicone gel. In many cases, after a few years, the tissue surrounding these implants stiffens, necessitating surgical removal. One effort to overcome this problem is to wrap a polyurethane foam around the prosthesis to allow tissue ingrowth and thus prevent tissue hardening. The polyurethane foams currently used, however, are known to biodegrade after implantation. Thus, a need exists for the development of a biostable tissue ingrowth platform which has improved cellula infiltration characteristics while simultaneously not being subject to extensive long term biodegradation.
The currently used medical polyurethanes are usually polyether-based polyurethanes in spite of studies which have shown that ether groups especially ethers in which the methyl group is in the alpha position to the ether oxygen is susceptible to in vivo oxidation. Oxidation occurs and causes eventual chain cleavage, leading to significant reductions in molecular weight at the surface and eventual surface fissuring. Polyurethanes made by using lower amounts of the ether component per weight of polymer have been shown to produce a polymer having increased biostability and exhibiting less surface fissuring after implantation for several months.
Biocompatible polyurethanes soluble in organic solvents are disclosed in Ger. Offen. DE 3, 643,465 (G. Wick, 1988). These polyurethanes are claimed to be compatible with blood and tissue and useful as catheters, prostheses, and in the production of pacemaker housings. The polyurethanes are produced by reacting an aliphatic or cycloaliphatic macrodiol with 3-33 molar proportion of a cycloaliphatic diisocyanate to give a pre-adduct having NCO groups followed by chain elongation of the pre-adduct with a mixture of the macrodiol and a specific lower aliphatic diol, i.e. trimethylhexanediol. The macrodiol may be 1, 6-hexanediolpolycarbonate carbonate. The resultant thermoplastic polymers have tensile strengths of about 4750-5200 psi, moduli of elasticity of about 300 psi or higher, and ultimate elongations of about 460-520%.
A thin abrasion-resistant polyurethane coating for transparent polycarbonate substates has been prepared by reaction of a polycarbonatediol with an aliphatic diisocyanate and then hardened with a trifunctional crosslinking agent. (Ger. Offen. DE 3,323,684)
Polyurethane elastomers for use a coating with superior durability have been prepared from a polyesther polyol derived from 1,10- decanedicarboxylic acid and a polycarbonate polyol by reaction with polyisocyanates and optionally with chain extenders. (Japan Kokai 57/31919, 1982)
Polycarbonate diols have been used in the manufacture of polycarbonate-polyurethanes for bilayer safety glass automobile windshields by polymerization of an aliphatic diol with a dialkyl carbonate in the presence of an alkali metal-free titanium compound. (U.S. Pat No. 4,160,853)
There exists a substantial need for a family of biostable polyurethane polymers some members of which can be used to produce improved insulating compositions for pacemaker leads, small diameter vascular grafts, and tissue ingrowth platforms having improved cellular infiltration characteristics for mammary prostheses.
It is an object of the present invention to provide such polyurethanes, particularly polyurethanes which may be conventionally steam sterilized.
It is a further object to produce a biostable polyurethane having a tensile strength in excess of 4000 psi and an elastic modulus of less than about 200 psi.